The proposed study is concerned with an evaluation of the antiarrhythmic activity of quaternary ammonium compounds in animals with experimentally-induced arrhythmias. Several new compounds related to propranol, lidocaine and bretylium have been synthesized in this laboratory and have been examined for potential antiarrhythmic activity against digitalis-induced arrhythmias as well as rhythm disorders associated with acute myocardial infarction. In addition, all compounds are examined for antifibrillatory activity. The detailed cardiovascular pharmacology of these agents will be explored. Interest will be centered on their spectrum of antiarrhythmic activity as well as upon their hemodynamic effects and their electrophysiologic actions. An attempt will be made to better understand the relationships between chemical structure and antiarrhythmic activity. Present studies indicate that such a relationship does exist and that conversion of an active antirarrhythmic drug to its quaternary ammonium derivative increases its antiarrhythmic spectrum and reduces its unwanted effects upon the cardiovascular and central nervous systems. The primary objective will be to obtain a drug that is effective as an antiarrhythmic agent, especially when tested against arrhythmias due to myocardial ischemia, but has minimal hemodynamic effects and undesirable electrophysiologic actions.